Global vs. Focal Neuroimaging Markers of Dementia Risk

描述(由申请人提供)：我们的目标是使用自动脑MRI读取技术，自动标记路径(ALP)，识别和量化阿尔茨海默病(AD)的特定神经成像标记物。ALP是一种可靠、易于操作、完全自动化的技术，可以生成局部和全局的大脑体积测量。这个独立的项目建议对1997-99年间在匹兹堡获得的532个大脑磁共振成像进行二次分析，作为心血管健康研究(CHS；N01HC85082)的一部分，这是一项调查老年人心血管危险因素的多点观察性研究。CHS参与者接受了详细的痴呆症评估，作为CHS认知研究的一部分(CHS-CS；R01AGO15928)。我们的项目将利用从1989年到目前为止收集的丰富的流行病学数据，包括洛佩兹博士在匹兹堡进行的痴呆症后续评估(R01AG020098)。大脑的碱性磷酸酶体积测量将丰富CHS-CS数据集，并将提供给其他CHS研究人员。我们认为，ALP-衡量全局性和局灶性萎缩(海马和内侧颞叶)的指标：1)区分认知正常的老年人和那些受AD或轻度认知障碍影响的老年人；2)比传统的CHS-CS脑MRI指标(脑室和白质分级)更好地区分痴呆症病例；3)区分在接下来的5年内转为痴呆症的认知正常成年人与那些转为MCI或保持认知正常的老年人。这一应用程序的优势包括：匹兹堡即时提供532个大脑核磁共振成像，1989年至今记录良好的痴呆症病例，当地支持使用碱性磷酸酶，广泛的人口统计学、遗传学和临床数据。根据NIA阿尔茨海默氏症倡议的最终共识，我们将评估新的和传统的脑MRI读取方法的测量方法的融合有效性，并将测试当特定的神经成像生物标记物包括在诊断标准中时，痴呆症的诊断是否可以改善。我们还计划优化和支持其他研究人员使用ALP方法。这项建议的结果将为未来的RO1应用程序奠定基础，该应用程序将在3000多名社区卫生服务参与者中评估痴呆症风险的神经成像标记物，这些参与者有重复的磁共振成像和超过15年的痴呆症随访数据。

DESCRIPTION (provided by applicant): Our goal is to identify and quantify specific neuroimaging markers of Alzheimer Disease (AD) using an automated brain MRI reading technique, the automated labeling pathway (ALP). ALP is a reliable, easy to operate, fully automated technique that generates regional and global volumetric measures of the brain. This self-contained project proposes secondary analysis of 532 brain MRIs acquired in Pittsburgh in 1997-99 as part of the Cardiovascular Health Study (CHS; N01HC85082), a multisite observational study to investigate cardiovascular risk factors in the elderly. CHS participants received a detailed dementia evaluation as part of the Cognition Study of the CHS (CHS-CS; R01AGO15928). Our project will take advantage of the wealth of epidemiologic data collected from 1989 to date, including the follow-up dementia evaluation conducted in Pittsburgh by Dr. Lopez (R01AG020098). ALP volumetric measures of the brain will enrich the CHS-CS dataset and will be available to other CHS investigators. We propose that ALP- measures of global and focal atrophy (hippocampal and medial temporal lobe): 1) differentiate older individuals who are cognitively normal, vs. those who are affected by AD or Mild Cognitive Impairment; 2) discriminate cases of dementia better than conventional CHS-CS brain MRI measures (ventricular and white matter grade); 3) discriminate those cognitively normal adults who convert to dementia over the following 5 years vs. those who convert to MCI or remain cognitively normal. The strengths of this application include: immediate availability of 532 brain MRIs in Pittsburgh, well documented cases of dementia from 1989 to- date, local support for the use of ALP, extensive demographic, genetic and clinical data. In accordance to the Final Consensus of the NIA Alzheimer's initiative, we will evaluate the convergent validity of measures from novel and conventional brain MRI reading methods, and will test if diagnosis of dementia can improve when specific neuroimaging biomarkers are included in the diagnostic criteria. We also plan to optimize and support the use of the ALP method by other investigators. The results of this proposal will lay a foundation for a future RO1 application to assess neuroimaging markers of dementia risk in a sample of over 3,000 CHS participants, for whom repeated MRIs and over 15 years follow up data on dementia are available.